18F is the isotope of choice for many PET cancer imaging applications. It is a positron emitter having (i) a low trajectory energy (0.635 MeV), which allows for good signal resolution, (ii) a moderate half-life (˜110 minutes) and, (iii) is readily generated in a cyclotron from the stable element, 19F.
PET imaging agents are often based on a labeled biomolecule. An example is fluorodeoxyglucose (FDG). Since the high energy particle bombardment used to produce 18F will destroy complex organic molecules, 18F is first made as a fluoride in a cyclotron and subsequently attached to a biomolecule to be used as the imaging agent. Also, conditions used to incorporate 18F into other molecules are often too harsh for direct labeling of a biomolecule. Therefore, 18F is usually introduced into a precursor (such as an arylfluoride) that is then subsequently appended to a larger molecule. Such multi-step procedures result in delay from initial isotope production to use of a particular imaging agent with consequent loss in specific radioactivity.
PCT Application published as WO 2005/0077967 summarizes some of the known methodologies for incorporating 18F into imaging agents and describes a new approach which makes use of boron or silicon as acceptors capable of binding several 18F atoms, thus increasing the density of positron emitters in the resulting imaging agent. Also, the use of boronic acids/esters as an 18F acceptor circumvented the previous practice of generating arylfluorides in multi-step procedures.